title: [Investigation of chemotherapy based on enzyme expression and drug sensitivity test in colorectal cancer].
abstract: In colorectal cancer (CRC), 5-fluorouracil (5-FU) has been a basic chemotherapeutic agent. Orotate phosphoribosyltransferase (OPRT) and thymidine phosphorylase (TP) are essential enzymes for activation of 5-FU. Dihydropyrimidine dehydrogenase (DPD) is an enzyme for degradation. The feasibility of individualized chemotherapy was studied using the enzyme expression and drug sensitivity test.
  
  
  METHODS
  The study included 160 surgical patients (stage II to IV). OPRT, TP, and DPD expressions, assessed with immunohistochemistry, were evaluated in relation to clinicopathological features and patient survival. We assessed 5-FU sensitivity using the collagen gel droplet. Embedded culture-drug sensitivity test(CDDST). The area under the concentration curve (AUC) and growth inhibition curve (IR) were combined in the AUC-IR curve, according to which the individual AUC(IR₅₀) was calculated. Durations to achieve AUC(IR₅₀) were calculated using AUC(₂₄hr) values in UFT and S-1.
  
  
  RESULTS
  TP and DPD expression were positively associated with CRC progression and related with poor prognosis, although OPRT expression was negatively associated with CRC progression and related with better prognosis. Patient survival was best in patients with OPRT (+) DPD (-), and worst in those with OPRT (-) DPD (+). Individual AUC(IR₅₀) ranged from less than 100 mg·hr/mL to more than 10,000 mg·hr/mL. In the chemotherapy with UFT, 55% of patients achieved AUC(IR₅₀) within 6 months, 13% of patients achieved it 6 to 12 months, another 13% of patients in 12 to 24 months, and the other 19% after 24 months of chemotherapy. In the chemotherapy with S-1, 31% of patients achieved AUC(IR₅₀) within 1 course, 15% in 1 to 2 courses, another 23% in 2 to 6 courses and the other 31% of patients achieved AUC(IR₅₀) after 6 courses.
  
  
  CONCLUSIONS
  The present results suggest that patients' prognosis may be improved with selection of an anti-cancer drug based on the 5-FU metabolizing enzyme expressions and prognostic factors. CD-DST may predict the duration of chemotherapy.
authors.affiliation: Dept. of Surgery, Osaka North Japan Post Hospital, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Tokunaga
authors.forename: Takanori
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012680:Sensitivity and Specificity
chemical_list: D000970:Antineoplastic Agents